Drug development and disease molecular research tend to rely on large numbers of animals which must be sacrificed in order to determine a compound's effects. This process is time consuming and costly. However, small animal imaging methods are non-invasive, enabling researchers to use the same animal repeatedly in longitudinal studies and reduce development time and costs. One important imaging modality is micro Computed Tomagraphy (CT). Micro-CT is capable of revealing exquisite anatomical detail with high spatial resolution in the mouse; this is important for evaluating phenotype changes that occur in genetically modified animals. Use of micro-CT is also valuable in evaluating tumor kinetics, i.e., growth or reduction with chemotherapy. We propose to develop a novel CT system for small-animal imaging which uses a photon-counting approach with x-ray energy-discrimination capabilities and simultaneous detection of all photon energies. Our technology is based on use of two-dimensional CdZnTe (CZT) detector pixel arrays flip-chip bonded directly to a readout integrated circuit (1C) chip with a matching channel array. Such an x-ray detection system comes at an excellent time when several companies are developing contrast agents for mouse investigators. The use of multiple energy detection suggests the possibility of multi contrast agent evaluation in an animal during a single CT scan. In Phase I, we will investigate the feasibility of this innovative concept through experiments using existing channel-array chips and CZT pixel detectors, studies of such within a test micro-CT platform and computer simulations for the future readout chip. We will also develop the requirements and preliminary design specifications for the new chip and CZT pixel array as well as the envisioned photon-counting micro-CT system. At the end of Phase I, feasibility will be demonstrated and a preliminary design of the detector system will be ready. In Phase II we plan to design, fabricate and test a new readout chip, mount it to a suitable detector array, and build detector modules for a micro-CT system. The imaging capabilities and performance of this instrument will be determined and characterized. Our proposed effort targets the development of a CT system for small-animal imaging as a tool for drug discovery and disease research. It can however be adapted to diagnostic imaging of humans or to industrial imaging, thus greatly enhancing both the public benefits and commercial potential of the proposed project.